P1298: THE EFFICACY AND SAFETY OF MODIFIED MELPHALAN AND BUSULFAN-BASED CONDITIONING REGIMEN FOR ALLOGENEIC-HSCT IN REFRACTORY/RELAPSED OR PERSISTENT MRD POSITIVITY AML PATIENTS
Authors: Erlie Jiang, Shulian Chen, Xiaoyu Zhang, Weihua Zhai, Ting Niu, Yajing Xu, Guangxun Gao, Shengjin Fan, Zeping Zhou, Fang Zhou, LI Liu, Wei Yang, Qifa Liu, XI Zhang, Hai Bai, Rui XI, Yi He, Sizhou Feng, Mingzhe Han
Journal: HemaSphere (2023)

Topic: 22. Stem cell transplantation - Clinical Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only potentially curative treatment for patients with refractory/relapsed (R/R) acute myeloid leukemia (AML). However, the long-term survival results are suboptimal. Optimization of the conditioning regimen is needed to eradicate leukemia blasts and reduce early relapse. In this study, we made refinements in the conditioning regimen with both melphalan and busulfan, namely MCBC (the combination of melphalan, cladribine, busulfan, and cyclophosphamide). We aim to investigate the efficacy and safety of MCBC conditioning regimen for allo-HSCT in R/R AML patients, including patients with persistent minimal residual disease (MRD) positive.. Aims: We aim to investigate the efficacy and safety of MCBC conditioning regimen for allo-HSCT in R/R AML patients, including patients with persistent minimal residual disease (MRD) positive. Methods: This prospective multi-center clinical trial was conducted in 13 tertiary hospitals in China, and enrolled R/R AML patients, including patients with MRD persistent positive, underwent allo-HSCT from July 2020 to October 2022 (ChiCTR Registration ID: ChiCTR2000029936). The protocol was approved by institutional review boards at participating centers. All patients enrolled received MCBC preconditioning regimen: melphalan 60mg/m2/d, day -9~-8, cladribine 5mg/m2/d, day -7~-5, busulfan 3.2mg/kg/d, day -5~-3, cyclophosphamide 30mg/kg/d, day -2~-1. Rabbit ATG was added in haploid-identical and unrelated-matched donor transplantation. FK506/CsA +short course MTX±MMF was mostly used to prevent graft-versus-host disease（GVHD）. A post-transplantation consolidation treatment was provided whenever possible, including low-dose azacytidine, venetoclax, or FLT3 inhibitors. Probabilities of OS, DFS were calculated by Kaplan-Meier method. COX regression model was used for multivariate analysis. Results: This multicenter MCBC trial prospectively enrolled 97 patients, with median age 36 (ranged 13–58 years). We included 77 R/R AML and 20 patients with MRD persistent positive. Only 26 patients achieved MRD clearance before transplantation. Haplo-identical-donor HSCT (HID-HSCT) was the predominance HSCT type (n=65, 67.01%). Mucositis was the main reported regimen-related toxicity, mostly were mild and well tolerated. No graft failure was documented. All patients achieved hematology complete remission (CR) (100%) and 88.66% achieved MRD clearance on reconstitution day, indicating profound anti-leukemia capacity of MCBC regimen. The cumulative incidence of II to IV acute GVHD was 57.4±5.17%. With a median follow-up of 277（48-875）days, the estimated one-year overall survival (OS), relapse-free survival (RFS) and NRM of all patients were 71.8±5.2%, 66.4±5.3% and 10.8±3.7% respectively. The one-year cumulative incidence of relapse was 24.5±4.9%. Survival analysis using by Kaplan-Meier method was performed. It indicated high blast burden (blast≥20%) at HSCT, CMV reactivation and absence of opportune maintenance therapy post HSCT were significant independent risk factors. Competitive risk modal analysis for multivariate analysis also confirms the results. Summary/Conclusion: Our study confirms the excellent anti-leukemic capacity and good acceptable toxicity of MCBC conditioning regimen in R/R AML. Furthermore, it is important to decrease leukemic blast burden pre-HSCT and perform maintenance treatment after transplantation as soon as possible.Keywords: Allogeneic hematopoietic stem cell transplant, relapsed/refractory, Acute myeloid leukemia, Conditioning